Leflunomide in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT02509052 | Completed Phase 1 Results DMC

• 2 other identifiers: 15140NCI-2015-01181
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of leflunomide in treating patients with multiple myeloma that has come back (relapsed) or has not responded to previous treatment (refractory). Leflunomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

• MTD, Defined as the Highest Dose in Which =< 1/6 Patients Experience a Dose-limiting Toxicity, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03

  Observed toxicities will be summarized, for all dose levels, in terms of type (organ affected or laboratory determination), severity, time of onset, duration, serum concentration of the active leflunomide metabolite, probable association with the study treatment and reversibility or outcome.

  28 days

• Best Overall Response Rate: Proportion of Patients Reaching CR by IMWG Criteria

  Stringent complete response \[sCR\]/complete response \[CR\]/very good partial response \[VGPR\]/or partial response \[PR\]), assessed by International Myeloma Working Group (IMWG) criteria.

  From the start of treatment until disease progression/recurrence, assessed up to 48 months

Secondary Outcomes (3)

• Clinical Benefit Response Rate (sCR/CR/VGPR/Partial Response [PR]/Minimal Response [MR] or Stable Disease [SD]), Assessed by IMWG Criteria

  From the start of treatment until disease progression/recurrence, assessed up to 48 months

• Response Duration

  Assessed up to 48 months

• Response Duration

  Assessed at ninety days.

Study Arms (3)

Arm 1: 20 mg leflunomide

EXPERIMENTAL

Patients receive 20 mg leflunomide PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Leflunomide; Other: Pharmacological Study

Arm 2: 40 mg leflunomide

EXPERIMENTAL

Patients receive 40 mg leflunomide PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Leflunomide; Other: Pharmacological Study

Arm 3: 60 mg leflunomide

EXPERIMENTAL

Patients receive 60 mg leflunomide PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Leflunomide; Other: Pharmacological Study

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm 1: 20 mg leflunomide; Arm 2: 40 mg leflunomide; Arm 3: 60 mg leflunomide

Leflunomide DRUG

Given PO

Also known as: Arava, SU101

Arm 1: 20 mg leflunomide; Arm 2: 40 mg leflunomide; Arm 3: 60 mg leflunomide

Pharmacological Study OTHER

Correlative studies

Arm 1: 20 mg leflunomide; Arm 2: 40 mg leflunomide; Arm 3: 60 mg leflunomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must have the ability to understand and the willingness to sign a written informed consent
• Patients must have a life expectancy of \> 3 months
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Patients must have a diagnosis of multiple myeloma
• Serum M-protein \>= 0.5 g/dL
• Urine M-protein \>= 200 mg/24 hr
• Serum free light chain \>=10 mg/dL provided the free light chain (FLC) ratio is abnormal
• % plasma cells in bone marrow
• Patients must be relapsed or are refractory to at least 3 prior lines of therapy, including both a proteasome inhibitor an immunomodulatory drug (IMiD), and for whom a transplant is not recommended (induction therapy and stem cell transplant +/- maintenance will be considered as one regimen)
• At least 2 weeks from prior therapy to time of start of treatment; prior therapy includes steroids (except prednisone or equivalent - up to 10 mg per day is allowed)
• Platelet count \>= 50,000/uL; platelet transfusions are not allowed within 14 days of platelet assessment
• Absolute neutrophil count (ANC) \>= 1000/mm\^3; growth factor is not permitted within 14 days of neutrophil assessment
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.0 x upper limit of normal (ULN)
• Total Bilirubin \< 1.5 x ULN
• Calculated creatinine clearance (CrCl) \>= 30 mL/min per 24 hour urine collection or the Cockcroft-Gault formula

You may not qualify if:

• Prior treatment with leflunomide
• Current or planned use of other investigational agents, or concurrent biological, chemotherapy, or radiation therapy during the study treatment period
• Current or planned growth factor or transfusion support until after initiation of treatment; if growth factor or transfusion support is provided between screening and start of treatment, the participant will no longer be eligible
• Prior diagnosis of rheumatoid arthritis
• Prior allogenic transplant
• Acute active infection requiring systemic therapy within 2 weeks prior to enrollment
• Pre-existing liver disease
• Known human immunodeficiency virus (HIV) infection
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to leflunomide or cholestyramine
• Non-hematologic malignancy within the past 3 years aside from the following exceptions:
• Adequately treated basal cell or squamous cell skin cancer
• Carcinoma in situ of the cervix
• Prostate cancer \< Gleason grade 6 with a stable prostate specific antigen (PSA)
• Successfully treated in situ carcinoma of the breast
• Clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or the patient's ability to give informed consent

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Related Publications (1)

• Rosenzweig M, Palmer J, Tsai NC, Synold T, Wu X, Tao S, Hammond SN, Buettner R, Duarte L, Htut M, Karanes C, Nathwani N, Pichiorri F, Sahebi F, Sanchez JF, Chowdhury A, Krishnan A, Forman SJ, Rosen ST. Repurposing leflunomide for relapsed/refractory multiple myeloma: a phase 1 study. Leuk Lymphoma. 2020 Jul;61(7):1669-1677. doi: 10.1080/10428194.2020.1742900. Epub 2020 Apr 8.

  PMID: 32268821 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Leflunomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Michael Rosenzweig, MD
• Organization: Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope, Duarte, CA 91010

mrosenzweig@coh.org

626-218-2405

Study Officials

• Michael Rosenzweig

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The phase I portion will implement a modified rolling six dose escalation design, a more conservative version of the rolling six design of Skolnik, et al., for enrollment with dose escalation, de-escalation, or expansion of a cohort on the basis of the occurrence of dose limiting toxicities (DLTs) during cycle 1. The starting dose of leflunomide is 20mg daily, with the intention to test up to 60mg daily. Escalation will proceed in increments of 20mg/daily; de-escalation will proceed in decrements of 10mg/day. Leglunomide is administered with a loading dose of 100 mg for the 1st three doses.

Study Record Dates

• First Submitted: July 23, 2015
• First Posted: July 27, 2015
• Study Start: December 2, 2015
• Primary Completion: September 18, 2018
• Study Completion: June 9, 2022
• Last Updated: October 10, 2023
• Results First Posted: October 10, 2023

Record last verified: 2023-09

Locations

US (1)